Background/Aims: Recent studies have highlighted the importance of gene by diet interactions in contributing to risk factors of metabolic syndrome. We used a consomic rat panel, in which a chromosome of the Brown Norway (BN) strain is introgressed onto the background of the Dahl salt-sentitive (SS) strain, to test the hypothesis that these animals will be useful for dissecting gene by diet interactions involved in metabolic syndrome. Methods: We placed the parental SS and BN strains on a low-fat/high-carbohydrate (LF) or high-fat/low-carbohydrate (HF) diet for 22 weeks and measured several indices of metabolic syndrome. We then investigated the effect of diet in eight consomic rat strains. Results: We show that the HF diet resulted in significantly increased levels of fasting plasma cholesterol and triglycerides in the SS strain, with no effect in the BN. Both strains responded to the HF diet with slight increases in body weight. SSBN8 was the only consomic strain that resembled that of the BN, with low levels of fasting cholesterol and triglycerides even on the HF diet. Conclusions: These results indicate that BN chromosome 8 harbors a gene or genes that confer protection against dyslipidemia caused by the HF diet.

1.
Alberti KG, et al: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640–1645.
2.
Groop L, Orho-Melander M: The dysmetabolic syndrome. J Intern Med 2001;250:105–120.
3.
Pereira MA, et al: Preventing and managing cardiometabolic risk: the logic for intervention. Int J Environ Res Public Health 2009;6:2568–2584.
4.
Ruchat SM, et al: Evidence of interaction between type 2 diabetes susceptibility genes and dietary fat intake for adiposity and glucose homeostasis-related phenotypes. J Nutrigenet Nutrigenomics 2009;2:225–234.
5.
Laursen L: Interdisciplinary research: Big science at the table. Nature 2010;468:S2–S4.
6.
Krauss RM: Dietary and genetic probes of atherogenic dyslipidemia. Arterioscler Thromb Vasc Biol 2005;25:2265–2272.
7.
Ahmed F: Health: Edible advice. Nature 2010;468:S10–S12.
8.
Ghibaudi L, et al: Fat intake affects adiposity, comorbidity factors, and energy metabolism of sprague-dawley rats. Obes Res 2002;10:956–963.
9.
Dobrian AD, et al: Development of hypertension in a rat model of diet-induced obesity. Hypertension 2000;35:1009–1015.
10.
West DB, et al: Dietary obesity in nine inbred mouse strains. Am J Physiol 1992;262(6 Pt 2):R1025–R1032.
11.
Svenson KL, et al: Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations. J Appl Physiol 2007;102:2369–2378.
12.
Schemmel R, Mickelsen O, Gill JL: Dietary obesity in rats: Body weight and body fat accretion in seven strains of rats. J Nutr 1970;100:1041–1048.
13.
Fearnside JF, et al: Phylometabonomic patterns of adaptation to high fat diet feeding in inbred mice. PLoS One 2008;3:e1668.
14.
Pravenec M, et al: Genetic analysis of ‘metabolic syndrome’ in the spontaneously hypertensive rat. Physiol Res 2004;53(suppl 1):S15–S22.
15.
Bilusic M, et al: Mapping the genetic determinants of hypertension, metabolic diseases, and related phenotypes in the lyon hypertensive rat. Hypertension 2004;44:695–701.
16.
Seda O, et al: Metabolic characterization of insulin resistance syndrome feature loci in three brown Norway-derived congenic strains. Folia Biol (Praha) 2002;48:81–88.
17.
Plum L, et al: Characterisation of the mouse diabetes susceptibilty locus Nidd/SJL: islet cell destruction, interaction with the obesity QTL Nob1, and effect of dietary fat. Diabetologia 2002;45:823–830.
18.
Chadt A, et al: Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 2008;40:1354–1359.
19.
Cowley AW Jr, Roman RJ, Jacob HJ: Application of chromosomal substitution techniques in gene-function discovery. J Physiol 2004;554(Pt 1):46–55.
20.
Mattson DL, et al: Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease. Am J Physiol Renal Physiol 2008;295:F837–F842.
21.
Mattson DL, et al: Chromosomal mapping of the genetic basis of hypertension and renal disease in FHH rats. Am J Physiol Renal Physiol 2007;293:F1905–F1914.
22.
Gilibert S, et al: Implication of chromosome 13 on hypertension and associated disorders in Lyon hypertensive rats. J Hypertens 2009;27:1186–1193.
23.
Gilibert S, et al: Effects of chromosome 17 on features of the metabolic syndrome in the Lyon hypertensive rat. Physiol Genomics 2008;33:212–217.
24.
Snyder EE, et al: The human obesity gene map: the 2003 update. Obes Res 2004;12:369–439.
25.
Pausova Z, et al: Segment of rat chromosome 20 regulates diet-induced augmentations in adiposity, glucose intolerance, and blood pressure. Hypertension 2003;41:1047–1055.
26.
Reed DR, et al: Body fat distribution and organ weights of 14 common strains and a 22-strain consomic panel of rats. Physiol Behav 2011;103:523–529.
27.
Reaven GM, Twersky J, Chang H: Abnormalities of carbohydrate and lipid metabolism in Dahl rats. Hypertension 1991;18:630–635.
28.
Parks EJ, Hellerstein MK: Carbohydrate-induced hypertriacylglycerolemia: historical perspective and review of biological mechanisms. Am J Clin Nutr 2000;71:412–433.
29.
Sharma N, et al: High fructose diet increases mortality in hypertensive rats compared to a complex carbohydrate or high fat diet. Am J Hypertens 2007;20:403–409.
30.
Parks EJ, et al: Predictors of plasma triglyceride elevation in patients participating in a coronary atherosclerosis treatment program. J Cardiopulm Rehabil 2001;21:73–79.
31.
Pennacchio LA, et al: Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 2002;11:3031–3038.
32.
Hansotia T, et al: Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure. J Clin Invest 2007;117:143–152.
33.
Okere IC, et al: Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension. Hypertension 2006;48:1116–1123.
34.
Nagae A, et al: Effect of high fat loading in Dahl salt-sensitive rats. Clin Exp Hypertens 2009;31:451–461.
35.
Kim BH, Akoh CC, Lee BY: The effects of high dietary lard on hypertension development in spontaneously hypertensive rats. J Med Food 2010;13:1263–1272.
36.
Seda O, et al: Region of rat chromosome 8 determines complex nutrigenetic interactions under conditions of sucrose and cholesterol diets. Prague Med Rep 2006;107:251–260.
37.
Wallis RH, et al: Enhanced insulin secretion and cholesterol metabolism in congenic strains of the spontaneously diabetic (Type 2) Goto Kakizaki rat are controlled by independent genetic loci in rat chromosome 8. Diabetologia 2004;47:1096–1106.
38.
Pilia G, et al: Heritability of cardiovascular and personality traits in 6,148 Sardinians. PLoS Genet 2006;2:e132.
39.
Kathiresan S, et al: Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 2009;41:56–65.
40.
Aulchenko YS, et al: Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 2009;41:47–55.
41.
Rensen PC, van Dijk KW, Havekes LM: Apolipoprotein AV: low concentration, high impact. Arterioscler Thromb Vasc Biol 2005;25:2445–2447.
42.
Lai CQ, et al: Dietary intake of n-6 fatty acids modulates effect of apolipoprotein A5 gene on plasma fasting triglycerides, remnant lipoprotein concentrations, and lipoprotein particle size: the Framingham Heart Study. Circulation 2006;113:2062–2070.
43.
Liu KH, et al: Mesenteric fat thickness as an independent determinant of fatty liver. Int J Obes (Lond) 2006;30:787–793.
44.
Kloting N, et al: Insulin-sensitive obesity. Am J Physiol Endocrinol Metab 2010;299:E506–E515.
45.
Despres JP, et al: Abdominal obesity and the metabolic syndrome: contribution to global cardiometabolic risk. Arterioscler Thromb Vasc Biol 2008;28:1039–1049.
46.
Liu KH, et al: Mesenteric fat thickness is an independent determinant of metabolic syndrome and identifies subjects with increased carotid intima-media thickness. Diabetes Care 2006;29:379–384.
47.
Sato A, et al: Antiobesity effect of eicosapentaenoic acid in high-fat/high-sucrose diet-induced obesity: importance of hepatic lipogenesis. Diabetes 2010;59:2495–2504.
48.
Mondon CE, et al: Mechanism of hypertriglyceridemia in Dahl rats. Hypertension 1993;21:373–379.
49.
Roman RJ, et al: Consomic rats for the identification of genes and pathways underlying cardiovascular disease. Cold Spring Harb Symp Quant Biol 2002;67:309–315.
50.
Drenjancevic-Peric I, Frisbee JC, Lombard JH: Skeletal muscle arteriolar reactivity in SS.BN13 consomic rats and Dahl salt-sensitive rats. Hypertension 2003;41:1012–1015.
51.
Cowley AW Jr, et al: Brown Norway chromosome 13 confers protection from high salt to consomic Dahl S rat. Hypertension 2001;37(2 Part 2):456–461.
52.
James PT, Rigby N, Leach R: The obesity epidemic, metabolic syndrome and future prevention strategies. Eur J Cardiovasc Prev Rehabil 2004;11:3–8.
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